It is generally agreed that stem or progenitor cells have significant potential for improved therapies and curing degenerative diseases. Indeed, the question is not so much whether progenitor cells are a reservoir from which more specialized cells and tissues can be derived, but rather how cells can be coaxed into choosing a certain pathway. Indeed, one of the stated goals of RFA: EB-03-010 (Research Opportunities in Tissue Engineering) is "The Isolation of stem and progenitor cells and methods to promote targeted stimulation of proliferation and controlled differentiation, including evaluation of signaling pathways in differentiation and dedifferentiation". This grant application is aimed at exploring the use of the Wnt family of embryonic growth factors to address this question. The proposal is based on a recent breakthrough: Wnt proteins have been isolated, for the first time, a biologically active form. There is tantalizing evidence that Wnt signaling in vivo controls many developmental decisions, including the expansion of progenitor cells which have a predetermined fate. In preliminary experiments, it has been shown that Wnt proteins promote the proliferation of limb mesenchymal precursor cells and induce the expression of genes associated with regeneration. It is now proposed to explore in detail how isolated Wnt proteins can be used to manipulate mesenchymal precursor cells in culture, with the ultimate goal of using these important molecules as growth factors in tissue engineering. The ability to combine purified Wnt proteins with cells in culture and genomics offer a powerful approach to study the mechanism of cell fate choices and may lead to the use of a new class of reagents to manipulate progenitor cells.